This application will address two major issues limiting the effective application of human islet allo-transplantation: 1) decreased islet mass from procurement and implantation induced damage, and 2) allo- and tissue-specific immune destruction of transplanted islets. The investigators hypothesize that optimal recovery techniques combined with novel in vitro manipulations will produce superior islets for transplantation that will be resistant to destruction during the procurement and implantation phase of the transplant. They further believe that a short course immune modulation based around a monoclonal antibody specific for CD4 will be superior to long term immuno-suppression in preventing islet rejection. The investigators propose to use established techniques for islet isolation in concert with a novel in vitro islet modification (caspase inhibition) aimed at interrupting the events leading to islet apoptosis. They will implant these islets into patients treated with a non-depleting anti-CD4 monoclonal antibody. Other manipulations including DR haplotype shared transfusion will be used in competing cohorts of patients. Patients will be monitored for their immune responsiveness towards the islet allo-graft, and the islets will be evaluated by biopsy. The function of the islets will be evaluated to determine the success of their interventions.